KEGG   PATHWAY: ocu04217
Entry
ocu04217                    Pathway                                
Name
Necroptosis - Oryctolagus cuniculus (rabbit)
Description
Necroptosis is a programmed form of necrosis. It can be initiated by different stimuli, such as tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand (TRAIL), Fas ligand (FasL), interferon (IFN), LPS, viral DNA or RNA, DNA-damage agent and requires the kinase activity of receptor-interacting protein 1 (RIPK1) and RIPK3. Its execution involves ROS generation, calcium overload, the opening of the mitochondrial permeability transition pore, mitochondrial fission, inflammatory response and chromatinolysis. Necroptosis participates in many pathogenesis of diseases, including neurological diseases, retinal disorders, acute kidney injury, inflammatory diseases and microbial infections.
Class
Cellular Processes; Cell growth and death
Pathway map
ocu04217  Necroptosis
ocu04217

Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100008602  IFNG; interferon gamma precursor [KO:K04687]
100008609  FAS; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
100008724  PPIA; peptidyl-prolyl cis-trans isomerase A [KO:K03767] [EC:5.2.1.8]
100008748  PLA2G4A; cytosolic phospholipase A2 [KO:K16342] [EC:3.1.1.4]
100008751  VDAC1; voltage-dependent anion-selective channel protein 1 [KO:K05862]
100008752  VDAC3; voltage-dependent anion-selective channel protein 3 [KO:K15041]
100008801  CYBB; cytochrome b-245 heavy chain [KO:K21421] [EC:1.-.-.-]
100008972  PYGM; glycogen phosphorylase, muscle form [KO:K00688] [EC:2.4.1.1]
100008990  IL1B; interleukin-1 beta precursor [KO:K04519]
100009013  EIF2AK2; interferon-induced, double-stranded RNA-activated protein kinase [KO:K16195] [EC:2.7.11.1]
100009024  TLR3; toll-like receptor 3 precursor [KO:K05401]
100009088  TNF; tumor necrosis factor precursor [KO:K03156]
100009089  [KO:K01367] [EC:3.4.22.52]
100009092  CAPN2; calpain-2 catalytic subunit [KO:K03853] [EC:3.4.22.53]
100009114  ALOX15; polyunsaturated fatty acid lipoxygenase ALOX15 [KO:K00460] [EC:1.13.11.33]
100009250  IL1A; interleukin-1 alpha [KO:K04383]
100009254  FTL; ferritin light chain [KO:K13625]
100009414  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
100009473  VDAC2; voltage-dependent anion-selective channel protein 2 [KO:K15040]
100009497  TLR4; toll-like receptor 4 [KO:K10160]
100009597  [KO:K00522] [EC:1.16.3.1]
100101556  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
100101557  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
100101588  [KO:K01370] [EC:3.4.22.36]
100328558  H2AZ2; histone H2A.V [KO:K11251]
100328641  HMGB1; high mobility group protein B1 [KO:K10802]
100328700  XIAP; E3 ubiquitin-protein ligase XIAP [KO:K04725] [EC:2.3.2.27]
100337764  [KO:K05863]
100337888  [KO:K03171]
100337999  [KO:K04440] [EC:2.7.11.24]
100338097  [KO:K05131]
100338118  [KO:K16060]
100338152  [KO:K12196]
100338182  [KO:K11251]
100338505  [KO:K12192]
100338604  [KO:K05130]
100338694  [KO:K04079]
100338700  [KO:K15637] [EC:3.1.3.16]
100338814  [KO:K17065] [EC:3.6.5.5]
100338854  [KO:K05133]
100339324  [KO:K21634] [EC:3.4.19.12]
100340005  [KO:K09849]
100340120  [KO:K16060]
100340140  [KO:K12196]
100340517  [KO:K16342] [EC:3.1.1.4]
100340606  [KO:K05864] [EC:5.2.1.8]
100340697  [KO:K11251]
100340775  [KO:K16342] [EC:3.1.1.4]
100340798  [KO:K12191]
100341033  PLA2G4E; cytosolic phospholipase A2 epsilon [KO:K16342] [EC:3.1.1.4]
100341237  [KO:K16342] [EC:3.1.1.4]
100341507  [KO:K04515] [EC:2.7.11.17]
100341677  [KO:K11251]
100341787  [KO:K05132]
100342157  [KO:K14381]
100342308  [KO:K10802]
100342407  [KO:K00688] [EC:2.4.1.1]
100342451  [KO:K04515] [EC:2.7.11.17]
100342635  [KO:K11251]
100342664  [KO:K04440] [EC:2.7.11.24]
100342931  [KO:K05415]
100342972  [KO:K05863]
100343113  [KO:K12197]
100343893  [KO:K11220]
100343925  [KO:K11251]
100343946  [KO:K10802]
100343960  [KO:K12196]
100344073  [KO:K04389]
100344146  [KO:K11222]
100344264  [KO:K11225]
100344432  [KO:K04693]
100344467  [KO:K11221]
100344622  [KO:K11219] [EC:2.7.10.2]
100344660  [KO:K11251]
100344695  [KO:K11251]
100345168  [KO:K11251]
100345205  [KO:K11251]
100345211  [KO:K12198]
100345225  TICAM2; TIR domain-containing adapter molecule 2 [KO:K05409]
100345253  [KO:K04725] [EC:2.3.2.27]
100345904  [KO:K15053]
100345939  [KO:K11251]
100346106  [KO:K03158]
100346477  [KO:K05863]
100346499  [KO:K11251]
100346929  [KO:K04440] [EC:2.7.11.24]
100346964  [KO:K04724]
100346975  [KO:K11251]
100347019  [KO:K11251]
100347336  [KO:K24070]
100347428  [KO:K00688] [EC:2.4.1.1]
100347474  [KO:K24782]
100347535  [KO:K11251]
100347560  [KO:K10630] [EC:2.3.2.31]
100347778  [KO:K04727] [EC:1.-.-.-]
100347889  [KO:K12194]
100348057  [KO:K05863]
100348267  [KO:K11224]
100348415  [KO:K11251]
100348420  [KO:K11974] [EC:2.3.2.31]
100348477  [KO:K04398] [EC:3.4.22.61]
100348485  [KO:K11251]
100348518  [KO:K11223]
100348744  [KO:K11251]
100348778  [KO:K04692]
100349506  [KO:K05862]
100349753  [KO:K12197]
100349768  [KO:K05863]
100350091  [KO:K11251]
100350259  [KO:K11859] [EC:3.4.19.12]
100350918  [KO:K11251]
100350932  [KO:K04982] [EC:2.7.11.1]
100350997  [KO:K11251]
100351029  [KO:K00261] [EC:1.4.1.3]
100352110  [KO:K12799]
100352594  [KO:K11217] [EC:2.7.10.2]
100352965  [KO:K02861] [EC:2.7.11.1]
100353094  [KO:K10802]
100353390  [KO:K05414]
100353691  [KO:K11251]
100353898  [KO:K12350] [EC:3.1.4.12]
100354572  [KO:K08601] [EC:3.4.19.12]
100354654  [KO:K05414]
100354802  [KO:K05863]
100355669  [KO:K05414]
100355675  [KO:K02159]
100355808  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
100355912  [KO:K05414]
100355991  [KO:K04726]
100356081  [KO:K12967]
100356237  [KO:K10802]
100356326  [KO:K05863]
100356419  [KO:K05414]
100356678  [KO:K05414]
100357194  [KO:K05414]
100357425  [KO:K11251]
100357708  [KO:K05414]
100357809  [KO:K12193]
100357913  [KO:K11251]
100358134  [KO:K04447] [EC:2.7.10.2]
100358690  [KO:K04079]
100358742  [KO:K11251]
100358889  [KO:K10802]
100359149  [KO:K10802]
100359274  [KO:K01915] [EC:6.3.1.2]
100533118  PLA2G4B; cytosolic phospholipase A2 beta [KO:K16342] [EC:3.1.1.4]
103345138  [KO:K11251]
103349397  [KO:K02161]
103351788  [KO:K11251]
108176001  [KO:K17595]
127482580  [KO:K12194]
127486194  [KO:K11218] [EC:2.7.10.2]
127486509  [KO:K12195]
127487650  [KO:K08601] [EC:3.4.19.12]
127488925  [KO:K11222]
127488928  [KO:K11220]
127489134  [KO:K12196]
127490017  [KO:K17595]
127490210  [KO:K11251]
127491150  [KO:K11221]
127492411  [KO:K12197]
Compound
C00002  ATP
C00027  Hydrogen peroxide
C00076  Calcium cation
C00195  N-Acylsphingosine
C00219  Arachidonate
C00305  Magnesium cation
C00319  Sphingosine
C00550  Sphingomyelin
C14592  N-Methyl-N'-nitro-N-nitrosoguanidine
C16844  Hydroxyl radical
Reference
  Authors
Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G
  Title
Molecular mechanisms of necroptosis: an ordered cellular explosion.
  Journal
Nat Rev Mol Cell Biol 11:700-14 (2010)
DOI:10.1038/nrm2970
Reference
  Authors
Brenner D, Blaser H, Mak TW
  Title
Regulation of tumour necrosis factor signalling: live or let die.
  Journal
Nat Rev Immunol 15:362-74 (2015)
DOI:10.1038/nri3834
Reference
  Authors
Conrad M, Angeli JP, Vandenabeele P, Stockwell BR
  Title
Regulated necrosis: disease relevance and therapeutic opportunities.
  Journal
Nat Rev Drug Discov 15:348-66 (2016)
DOI:10.1038/nrd.2015.6
Reference
  Authors
Ofengeim D, Yuan J
  Title
Regulation of RIP1 kinase signalling at the crossroads of inflammation and cell death.
  Journal
Nat Rev Mol Cell Biol 14:727-36 (2013)
DOI:10.1038/nrm3683
Reference
  Authors
Murphy JM, Vince JE
  Title
Post-translational control of RIPK3 and MLKL mediated necroptotic cell death.
  Journal
F1000Res 4:F1000 Faculty Rev-1297 (2015)
DOI:10.12688/f1000research.7046.1
Reference
  Authors
Vanden Berghe T, Linkermann A, Jouan-Lanhouet S, Walczak H, Vandenabeele P
  Title
Regulated necrosis: the expanding network of non-apoptotic cell death pathways.
  Journal
Nat Rev Mol Cell Biol 15:135-47 (2014)
DOI:10.1038/nrm3737
Reference
  Authors
Dondelinger Y, Hulpiau P, Saeys Y, Bertrand MJ, Vandenabeele P
  Title
An evolutionary perspective on the necroptotic pathway.
  Journal
Trends Cell Biol 26:721-32 (2016)
DOI:10.1016/j.tcb.2016.06.004
Reference
  Authors
Thapa RJ, Ingram JP, Ragan KB, Nogusa S, Boyd DF, Benitez AA, Sridharan H, Kosoff R, Shubina M, Landsteiner VJ, Andrake M, Vogel P, Sigal LJ, tenOever BR, Thomas PG, Upton JW, Balachandran S
  Title
DAI Senses Influenza A Virus Genomic RNA and Activates RIPK3-Dependent Cell Death.
  Journal
Cell Host Microbe 20:674-681 (2016)
DOI:10.1016/j.chom.2016.09.014
Reference
  Authors
Yuan J, Najafov A, Py BF
  Title
Roles of Caspases in Necrotic Cell Death.
  Journal
Cell 167:1693-1704 (2016)
DOI:10.1016/j.cell.2016.11.047
Reference
  Authors
Jorgensen I, Rayamajhi M, Miao EA
  Title
Programmed cell death as a defence against infection.
  Journal
Nat Rev Immunol 17:151-164 (2017)
DOI:10.1038/nri.2016.147
Reference
  Authors
Vandenabeele P, Declercq W, Van Herreweghe F, Vanden Berghe T
  Title
The role of the kinases RIP1 and RIP3 in TNF-induced necrosis.
  Journal
Sci Signal 3:re4 (2010)
DOI:10.1126/scisignal.3115re4
Reference
  Authors
Vanlangenakker N, Vanden Berghe T, Vandenabeele P
  Title
Many stimuli pull the necrotic trigger, an overview.
  Journal
Cell Death Differ 19:75-86 (2012)
DOI:10.1038/cdd.2011.164
Reference
  Authors
Moriwaki K, Chan FK
  Title
RIP3: a molecular switch for necrosis and inflammation.
  Journal
Genes Dev 27:1640-9 (2013)
DOI:10.1101/gad.223321.113
Reference
  Authors
Humphries F, Yang S, Wang B, Moynagh PN
  Title
RIP kinases: key decision makers in cell death and innate immunity.
  Journal
Cell Death Differ 22:225-36 (2015)
DOI:10.1038/cdd.2014.126
Reference
  Authors
Wegner KW, Saleh D, Degterev A
  Title
Complex Pathologic Roles of RIPK1 and RIPK3: Moving Beyond Necroptosis.
  Journal
Trends Pharmacol Sci 38:202-225 (2017)
DOI:10.1016/j.tips.2016.12.005
Reference
  Authors
Kupka S, De Miguel D, Draber P, Martino L, Surinova S, Rittinger K, Walczak H
  Title
SPATA2-Mediated Binding of CYLD to HOIP Enables CYLD Recruitment to Signaling Complexes.
  Journal
Cell Rep 16:2271-80 (2016)
DOI:10.1016/j.celrep.2016.07.086
Reference
  Authors
Goodall ML, Fitzwalter BE, Zahedi S, Wu M, Rodriguez D, Mulcahy-Levy JM, Green DR, Morgan M, Cramer SD, Thorburn A
  Title
The Autophagy Machinery Controls Cell Death Switching between Apoptosis and Necroptosis.
  Journal
Dev Cell 37:337-49 (2016)
DOI:10.1016/j.devcel.2016.04.018
Reference
  Authors
Xu G, Tan X, Wang H, Sun W, Shi Y, Burlingame S, Gu X, Cao G, Zhang T, Qin J, Yang J
  Title
Ubiquitin-specific peptidase 21 inhibits tumor necrosis factor alpha-induced nuclear factor kappaB activation via binding to and deubiquitinating receptor-interacting protein 1.
  Journal
J Biol Chem 285:969-78 (2010)
DOI:10.1074/jbc.M109.042689
Reference
  Authors
Jacobsen AV, Silke J
  Title
The importance of being chaperoned: HSP90 and necroptosis.
  Journal
Cell Chem Biol 23:205-7 (2016)
DOI:10.1016/j.chembiol.2016.02.003
Reference
  Authors
Gurung P, Man SM, Kanneganti TD
  Title
A20 is a regulator of necroptosis.
  Journal
Nat Immunol 16:596-7 (2015)
DOI:10.1038/ni.3174
Reference
  Authors
Feng N, Anderson ME
  Title
CaMKII is a nodal signal for multiple programmed cell death pathways in heart.
  Journal
J Mol Cell Cardiol 103:102-109 (2017)
DOI:10.1016/j.yjmcc.2016.12.007
Reference
  Authors
Zhivotovsky B, Galluzzi L, Kepp O, Kroemer G
  Title
Adenine nucleotide translocase: a component of the phylogenetically conserved cell death machinery.
  Journal
Cell Death Differ 16:1419-25 (2009)
DOI:10.1038/cdd.2009.118
Reference
  Authors
Thapa RJ, Nogusa S, Chen P, Maki JL, Lerro A, Andrake M, Rall GF, Degterev A, Balachandran S
  Title
Interferon-induced RIP1/RIP3-mediated necrosis requires PKR and is licensed by FADD and caspases.
  Journal
Proc Natl Acad Sci U S A 110:E3109-18 (2013)
DOI:10.1073/pnas.1301218110
Reference
  Authors
Thapa RJ, Basagoudanavar SH, Nogusa S, Irrinki K, Mallilankaraman K, Slifker MJ, Beg AA, Madesh M, Balachandran S
  Title
NF-kappaB protects cells from gamma interferon-induced RIP1-dependent necroptosis.
  Journal
Mol Cell Biol 31:2934-46 (2011)
DOI:10.1128/MCB.05445-11
Reference
  Authors
Sridharan H, Upton JW
  Title
Programmed necrosis in microbial pathogenesis.
  Journal
Trends Microbiol 22:199-207 (2014)
DOI:10.1016/j.tim.2014.01.005
Reference
  Authors
Cabon L, Galan-Malo P, Bouharrour A, Delavallee L, Brunelle-Navas MN, Lorenzo HK, Gross A, Susin SA
  Title
BID regulates AIF-mediated caspase-independent necroptosis by promoting BAX activation.
  Journal
Cell Death Differ 19:245-56 (2012)
DOI:10.1038/cdd.2011.91
Reference
  Authors
Baritaud M, Boujrad H, Lorenzo HK, Krantic S, Susin SA
  Title
Histone H2AX: The missing link in AIF-mediated caspase-independent programmed necrosis.
  Journal
Cell Cycle 9:3166-73 (2010)
DOI:10.4161/cc.9.16.12887
Reference
  Authors
Upton JW, Kaiser WJ
  Title
DAI Another Way: Necroptotic Control of Viral Infection.
  Journal
Cell Host Microbe 21:290-293 (2017)
DOI:10.1016/j.chom.2017.01.016
Reference
  Authors
Silke J, Rickard JA, Gerlic M
  Title
The diverse role of RIP kinases in necroptosis and inflammation.
  Journal
Nat Immunol 16:689-97 (2015)
DOI:10.1038/ni.3206
Reference
  Authors
Guo H, Kaiser WJ
  Title
ESCRTing Necroptosis.
  Journal
Cell 169:186-187 (2017)
DOI:10.1016/j.cell.2017.03.030
Reference
  Authors
Gong YN, Guy C, Olauson H, Becker JU, Yang M, Fitzgerald P, Linkermann A, Green DR
  Title
ESCRT-III Acts Downstream of MLKL to Regulate Necroptotic Cell Death and Its Consequences.
  Journal
Cell 169:286-300.e16 (2017)
DOI:10.1016/j.cell.2017.03.020
Reference
  Authors
Petrie EJ, Hildebrand JM, Murphy JM
  Title
Insane in the membrane: a structural perspective of MLKL function in necroptosis.
  Journal
Immunol Cell Biol 95:152-159 (2017)
DOI:10.1038/icb.2016.125
Reference
  Authors
Cai Z, Jitkaew S, Zhao J, Chiang HC, Choksi S, Liu J, Ward Y, Wu LG, Liu ZG
  Title
Plasma membrane translocation of trimerized MLKL protein is required for TNF-induced necroptosis.
  Journal
Nat Cell Biol 16:55-65 (2014)
DOI:10.1038/ncb2883
Reference
  Authors
Lawlor KE, Khan N, Mildenhall A, Gerlic M, Croker BA, D'Cruz AA, Hall C, Kaur Spall S, Anderton H, Masters SL, Rashidi M, Wicks IP, Alexander WS, Mitsuuchi Y, Benetatos CA, Condon SM, Wong WW, Silke J, Vaux DL, Vince JE
  Title
RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL.
  Journal
Nat Commun 6:6282 (2015)
DOI:10.1038/ncomms7282
Reference
  Authors
Shlomovitz I, Zargrian S, Gerlic M
  Title
Mechanisms of RIPK3-induced inflammation.
  Journal
Immunol Cell Biol 95:166-172 (2017)
DOI:10.1038/icb.2016.124
Related
pathway
ocu00250  Alanine, aspartate and glutamate metabolism
ocu04210  Apoptosis
ocu04668  TNF signaling pathway
ocu04922  Glucagon signaling pathway
KO pathway
ko04217   

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